Disturbed gastrointestinal motility and decreased interstitial cells of Cajal in diabetic db/db mice

Background and Aim: Diabetes mellitus (DM) often causes gastrointestinal dysmotility. Interstitial cells of Cajal (ICC), which express c-kit receptor tyrosine kinase (KIT), are considered the pacemaker cells for gastrointestinal movement. The present study was designed to determine the role of ICC in the pathogenesis of gastroenteropathy in type 2 DM. Methods: We examined C57BL/KsJ-db/db mice as a model for type 2 DM. Gastrointestinal motility was evaluated by measuring gastric emptying, whole gut transit time, and isometric tension of the isolated small intestine. The area of KIT-positive cells in the gastrointestinal tract was examined by image analysis of fluorescent immunohistochemistry. The mRNA expression of KIT ligand, stem cell factor (SCF), in the gastrointestinal tract was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: Compared with 12-week-old db/+m control mice, diabetic db/db mice of the same age exhibited delayed gastric emptying, prolonged whole gut transit time, irregular frequency of isometric tension in the small intestine, smaller areas of KIT-positive cells in the antrum, small intestine, and colon, and lower mRNA expression levels of SCF in the small intestine and colon. Conclusions: We demonstrated disturbed gastrointestinal motility in db/db mice with reduced areas of ICC and expression of SCF. Our results suggest the involvement of ICC in the gastroenteropathy of type 2 DM.